Method for evaluating and modifying biological activity

Abstract

Biological effects of agents for diagnostic or therapeutic use are evaluated by administration of the agents to transgenic animals which are transformed with heterologous DNA and which are immune tolerant to the expression product of the heterologous DNA. In a further embodiment, preparations that are immunogenic in the transgenic animal model are purified by reverse immunoaffinity chromatography on antibody obtained from responding transgenic animals.

I claim: 
     
       1. A method for detecting the immunogenicity of a potentially immunogenic polypeptide which comprises: (a) administering to a transgenic non-human mammal immunologically tolerant to a heterologous polypeptide as the result of the expression of a DNA sequence encoding said heterologous polypeptide, said DNA sequence having been introduced into said mammal or an ancestor of said mammal during an embryonic stage and being transcribed and continuously expressed under the control of a promoter, said potentially immunogenic polypeptide, wherein said potentially immunogenic polypeptide is a variant of said heterologous polypeptide; and   (b) detecting the presence of antibodies specific for said potentially immunogenic polypeptide, the presence of said antibodies being indicative of the immunogenicity of the polypeptide.   
     
     
       2. The method according to claim 1 wherein the potentially immunogenic polypeptide is produced by recombinant cell culture from cells expressing said heterologous polypeptide. 
     
     
       3. The method according to claim 1 wherein said heterologous polypeptide is a human polypeptide. 
     
     
       4. The method of claim 2 wherein said potentially immunogenic polypeptide is an amino acid sequence variant of said heterologous polypeptide. 
     
     
       5. The method according to claim 1 wherein said potentially immunogenic polypeptide is an amino acid sequence variant of said heterologous polypeptide. 
     
     
       6. The method according to claim 1 wherein said potentially immunogenic polypeptide is an interspecies variant of said heterologous polypeptide. 
     
     
       7. The method according to claim 1 wherein said potentially immunogenic polypeptide is a chemically modified variant of said heterologous polypeptide.